Acute treatment of migraine when triptans and ergots are contraindicated or not tolerated

Bert B. Vargas, MD, FAHS, FAAN Associate Professor Neurology and Neurotherapeutics UT Southwestern Medical Center Dallas, TX

Although triptans and ergots are migraine-specific acute treatments and considered to be the standard of care, they are contraindicated in a number of medical conditions including Prinzmetal’s angina, hemiplegic migraine, migraine with brainstem aura, ischemic stroke, coronary artery disease, peripheral vascular disease, and pregnancy. Despite a growing body of literature challenging many of these contraindications, they remain on the package labeling at the direction of the US Food and Drug Administration. Even in the absence of contraindications, triptans and ergots are also occasionally not tolerated by patients necessitating a knowledge of treatment alternatives for any provider caring for headache patients.

When selecting any medication, it is important to consider the level of supportive evidence in combination with individual patient-related factors including medical co-morbidities, medication sensitivities, potential medication interactions, and patient preference. All patients should be counseled regarding potential risks of any medications recommended.

When used frequently, many of the medications below have been associated with medication overuse headache and caution should be exercised with opiate, caffeine and butalbital containing medications given the additional potential for abuse, misuse, and dependence. Caution is recommended when using non-steroidal anti- inflammatory medications (NSAIDs) in patients at risk for complications from renal disease or hemorrhage (such as peptic ulcer disease or previous bariatric surgery) and regular use of NSAIDs has also been associated with an increased risk for cardiovascular events. Neuroleptics (including many of the antiemetics listed) are associated with dystonia and tardive dyskinesia and frequent use of steroid is associated with bone loss and iatrogenic Cushing’s syndrome. Despite these cautions, each of the medications below has a potential role for specific populations of patients.

Below is a tabulated summary of non-triptan, non-ergot acute treatment options based on recommendations by the American Headache Society (AHS) with additional information and recommendations by the Canadian Headache Society (CHS). All medications listed are oral formulations unless otherwise specified.

Established as Effective AHS CHS Medication Level of Recommendation Quality of Evidence Evidence Analgesic Acetaminophen A Strong High NSAIDs Aspirin A Strong High Diclofenac A Strong High Ibuprofen A Strong High Naproxen A Strong High Opioids Butorphanol IN* A Strong Low Combinations Acetaminophen/Aspirin/Caffeine A *Do not use except under exceptional circumstances per recommendation of CHS

Probably Effective AHS CHS Medication Level of Recommendation Quality of Evidence Evidence Antiemetics Droperidol IV B Prochlorperazine IV/IM B Metoclopramide IV B Chlorpromazine IV B Metoclopramide Strong Moderate NSAIDs Flurbiprofen B Ketoprofen B Ketorolac IV/IM B Other Magnesium Sulfate IV B Isometheptene B Combinations Codeine†/Acetaminophen B Weak Low Tramadol†/Acetaminophen B Weak Moderate †Not recommended for routine use per recommendation of CH

Possibly Effective AHS CHS Medication Level of Recommendation Quality of Evidence Evidence Antiepileptic Valproate IV C Antiemetic Domperidone Strong Low NSAIDs Phenazone C Opioid Butorphanol IM• C Meperidine IM• C Methadone IM• C Tramadol IV• C Codeine† C Weak Low Steroid Dexamthasone IV C Other Lidocaine IN C Butalbital* C Strong Low Combinations Butalbital*/Acetaminophen/ C Strong Low Caffeine/Codeine† Butalbital*/Acetaminophen/ C Strong Low Caffeine •No specified recommendations for non-oral opiates per CHS †Not recommended for routine use per recommendation of CHS *Do not use except under exceptional circumstances per recommendation of CHS

References: 1. Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the American Headache Society evidence assessment of migraine pharmacotherapies. Headache 2015;55:3-20. 2. Worthington I, Pringsheim T, Gawel MJ, et al. Targeted review: Medications for acute migraine treatment. Can J Neurol Sci 2013;40 suppl. 3:S10-S32.